Acquired resistance to the anti-proliferative effect of interleukin-1 and interleukin-6 is a recessive phenotype in A375 human melanoma cells.
The proliferation of human melanoma cell line A375-6 is inhibited by several cytokines, including interleukin-1 (IL-1) and interleukin-6 (IL-6). However, during a long period of culture, the cells progressively acquire resistance to IL-1 irrespective of functional IL-1 receptor expression. These cells constitutively produce IL-1alpha and IL-6, and also acquire resistance to IL-6. In order to investigate the mechanism of the acquired resistance to these cytokines, we performed somatic cell hybridization experiments. Parental cells for the construction of hybrid cells were rendered G418- or hygromycin B-resistant by transfection with expression vectors containing drug-resistant genes. Hybridization was conducted using IL-1-resistant subclones A375-R8 and R19 and an IL-1 highly sensitive clone C2-1, which was originally resistant but became sensitive to IL-1 upon transfection with a human type I IL-1 receptor (IL-1R) expression plasmid. Cells produced by hybridization of resistant cells and C2-1 cells appeared to be sensitive to IL-1 and IL-6. In contrast, production of IL-1 was augmented in the hybrid cells. These results suggest that resistance to IL-1 and IL-6 is a recessive phenotype, while production of IL-1 is dominant in melanoma cells.
Itoh
S
S
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuho, Japan.
Hayashi
H
H
Yang
D
D
Takii
T
T
Onozaki
K
K
D002455:Cell Division / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006822:Hybrid Cells; D007375:Interleukin-1 / Q000096:biosynthesis / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D010641:Phenotype; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha